Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from Entamoeba histolytica and Giardia lamblia Identifies Inhibitors of Their Trophozoite Growth Phase

Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure-based virtual screening of FDA-approved drugs was performed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL).     

Antiplatelet Effect and Selective Binding to Cyclooxygenase (COX) by Molecular Docking Analysis of Flavonoids and Lignans

The known flavonoids ginkgetin (1), taiwanhomoflavone A (2), taiwanhomoflavone B (3), and taiwanhomoflavone C (4) and eight known lignans: justicidin B (9), justicidin C (10), justicidin D (11), chinensinaphthol methyl ether (12), procumphthalide A (13), procumbenoside A (15), and ciliatosides A (16) and B (17) were isolated from Cephalotaxus wilsoniana and Justicia species, respectively. The antiplatelet effects of the above constituents on human platelet-rich plasma (PRP) were evaluated. Of the compounds tested on human PRP, compounds 1, 4, 9, and 11 showed inhibition of secondary aggregation induced by adrenaline. Compound 1 had an inhibitory effect on cyclooxygenase-1 (COX-1). Molecular docking studies revealed that 1 and the related compounds apigenin (5), cycloheterophyllin (6), broussoflavone F (7), and quercetin (8) were docked near the gate of active site of COX-1. It indicated that the antiplatelet effect of 1, 4, 9, and 11 is partially owed to suppression of COX-1 activity and reduced thromboxane formation. Flavonoids, 1, 5, 6, 7, and 8 may block the gate of the active site of COX-1 and interfere the conversion of arachidonic acid to prostaglandin (PG) H₂ in the COX-1 active site.     

人身意外伤害保险中介代理互联网销售系统的设计与实现

介绍了中国人寿保险股份有限公司湖南省分公司人身意外伤害保险中介代理互联网销售系统的设计与实现。该系统实现了人身意外伤害保险中介代理实时出单,以及与公司短险业务处理系统、单证管理系统的实时对接,具有较强的可扩展性和实用性。     

基于辅助视觉飞机空中加油对接优化过程仿真

研究飞机空中加油对接过程控制,提高对接准确性.飞机空中加油过程处在全程高速运动中,由于受油机在加油时处在前方大型加油机的尾流中受到强烈扰动,端口对接处在动态变化,传统的对接方法需要准确判断高速移动端口的准确位置,一旦尾流中受到强烈扰动,导致颠簸,对接误差距离计算较大.提出辅助视觉的飞机空中加油对接过程控制方法.统计飞机空中加油辅助视觉图像出现共现的频率,计算对应图像在所有图像中的共现度,通过运算获取对应图像的权重,实现关键帧图像定位,运用图像中心点空间位置,建立近距空中加油时的尾流流场对受油飞机的气动影响的数学模型,完成飞机空中加油接口的定位.实验结果表明,利用改进算法进行飞机空中加油对接过程控制,在飞机飞行震动较大的情况下,对接控制的准确性高于传统算法.     

苯并吡喃酮类化合物与Skp2蛋白的分子识别及其抑制机理

S期激酶相关蛋白2(S-phase kinase-associated protein 2,Skp2)与Skp1形成的蛋白质聚合物在调控癌细胞生长周期中发挥着重要作用,而苯并吡喃酮类抑制剂(简称BPC)可有效抑制Skp1-Skp2的形成,但其分子识别机制尚不明确.通过生物信息学统计分析已报道的Skp1-Skp2晶体结构,确定模拟体系后,首先用同源模建对其模拟体系缺失的结构进行补全;然后用分子对接方法获得Skp1-Skp2-BPC复合物模型并用于后续分子动力学模拟.计算结果表明:疏水相互作用是促使BPC特异性结合在由Skp2 W109、D110、L117、I120、R138和W139所构成口袋中的主要驱动力,自由能计算值与实验数据吻合较好.Skp2结合BPC后,结合口袋周围的氢键网络有所加强,口袋附近的溶剂化水分子数量明显减少,导致Skp1-Skp2的体系稳定性下降.体系构象成簇与运动性分析显示,Skp1-Skp2在结合BPC抑制剂后,Skp1的运动更加剧烈,这可能是BPC主要的抑制机理.     

基于机械臂运动的组合航天器惯性参数在轨辨识

随着空间技术发展,交会对接任务越来越多,服务航天器与目标航天器对接形成组合航天器后惯性参数会发生明显变化。因此,提出一种基于机械臂运动的组合航天器惯性参数在轨辨识方法。该方法可以分为2步:第一步辨识组合航天器的质量和质心;第二步辨识组合航天器的惯性张量。该方法优点是实现了质量、质心与惯性张量等辨识参数的相互解耦,不需要消耗航天器上宝贵的喷气燃料,仅需要测量航天器的速度,而不是加速度和力。仿真结果验证了方法的有效性。     

MoSz在空间对接摩擦材料烧结过程中的行为变化

采用粉末冶金技术制备了空间对接用铜基摩擦材料，利用X射线衍射及定量化学分析技术对MoS2在材料烧结过程中的变化行为及与其他组元之间的作用进行研究。结果表明，MoS2在加压烧结过程中存在三个方面的反应：在高温下分解成Mo和S,并造成了S元素的损失；与Cu作用形成了复杂的铜钼硫化合物；与Cu反应生成了Cu的硫化物，该类化合物具有与MoS2相类似的层状结构，有一定的润滑作用。MoS2高温分解后或MoS2与Cu反应产生的Mo元素与石墨反应形成了Mo的碳化物。另外，双飞粉的加入不仅与材料中的Mo元素作用形成CaMoO4并且改变了铜钼硫化合物、Cu的硫化物以及Mo的碳化物中各元素的麾尔比。     

基于嵌入式视觉的子机器人入舱方法

提出一种基于嵌入式视觉的子机器人入舱方法, 用于子母式机器人系统中对子机器人的回收. 子机器人基于自身嵌入式平台捕获和处理入口处的引导标识图像, 根据局部颜色排布特征快速提取出标识中心, 利用最小二乘法拟合水平颜色交界线的成像斜率, 基于成像斜率-视偏角模型判别出子机器人航向与入口平面的法线关系, 从而进行运动决策使二者重合以完成入舱. 该方法无需摄像头标定和航迹测量即可准确入舱, 仿真实验验证了所提出方法的有效性.

     

交会对接仿真电视图像TMO算法主观评价

通过对实时渲染仿真交会对接电视图像的主观评价,指出调和映射处理(TMO)算法的修正是提高仿真场景逼真度的方法.基于交会对接仿真电视图像TMO算法应用,分别针对S-curve算法、自适应对数算法和Reinhard算法设计了基于静态图像对比的亮度调和因子评价实验和基于动态场景对比的算法应用距离段评价实验,并对实验结果的均值、标准差以及HSD值进行了计算与分析;上述3种算法亮度调和因子分别为6.0,0.6和2.2,依次应用于远距离,中、近距离和靠拢距离时仿真电视图像有最佳评价和显示效果.实验结果表明,采用同种TMO算法处理的交会对接仿真图像动态场景真实感效果优于静态图像;在交会对接不同距离段内,仿真场景需要采用不同的TMO渲染方法.     

Virtual screening of eighteen million compounds against dengue virus: Combined molecular docking and molecular dynamics simulations study

Dengue virus is a major issue of tropical and sub-tropical regions. Dengue virus has been the cause behind the major alarming epidemics in the history with mass causalities from the decades. Unavailability of on-shelf drugs for the prevention of further proliferation of virus inside the human body results in immense number of deaths each year. This issue necessitates the design of novel anti-dengue drug. The protease enzyme pathway is the critical target for drug design due to its significance in the replication, survival and other cellular activities of dengue virus. Therefore, approximately eighteen million compounds from the ZINC database have been virtually screened against nonstructural protein 3 (NS3). The incremental construction algorithm of Glide docking program has been used with its features high throughput virtual screening (HTVS), standard precision (SP), extra precision (XP) and in combination of Prime module, induced fit docking (IFD) approach has also been applied. Five top-ranked compounds were then selected from the IFD results with better predicted binding energies with the catalytic triad residues (His51, Asp75, and Ser135) that may act as potential inhibitors for the underlying target protease enzyme. The top-ranked compounds ZINC95518765, ZINC44921800, ZINC71917414, ZINC39500661, ZINC36681949 have shown the predicted binding energies of −7.55, −7.36, −8.04, −8.41, −9.18 kcal/mol, respectively, forming binding interactions with three catalytically important amino acids. Top-docking poses of compounds are then used in molecular dynamics (MD) simulations. In computational studies, our proposed compounds confirm promising results against all the four serotypes of dengue virus, strengthening the opportunity of these compounds to work as potential on-shelf drugs against dengue virus. Further experimentation on the proposed compounds can result in development of strong inhibitors.